This is an ongoing project whose overall objective has beenm, and continues to be, the exploration of biochemical mechanisms responsible for temporally controlled expression of genes which specify proteins (particularly enzymes) critical to tissue specialization during mammalian ontogenesis. Such basic knowledge may contribute to the understanding, diagnosis and management of genetic and development abnormalities in man. In our studies over the past 16 years we have adopted the postnatal development of the rat liver and, histidase, as a model developmental system. We have already: described the developmental courses of this enzyme in the two tissues which express it; identified various hormonal regulators responsible for its development; and initiated studies on the biochemical mechanisms underlying endocrine influence on development of expression of the gene specifying histidase. Our recent success in developing a heterologous translational assay for functional histidase mRNA provides opportunities for gaining new and deeper insights concerning these mechanisms. We now plan: (1) inquiry into the molecular characteristics, function and genesis of a high molecular weight in vitro translation product, specified by rat liver RNA, and found to be immunologically related to the histidase subunit, (e.g., polyadenylation, molecular size, subcellular localization, structure and tissue distribution); (2) further inquiry as to whether alterations in functional histidase mRNA levels underlie changes in enzyme synthetic rate during development and in response to hormones; where indicated, possible translational control mechanisms will be investigated; (3) study of possible shifts in populations of histidase containing epidermal cells, during development and endocrine regualtion, employing immunocytochemistry; (4) attempts to develop a method for prenatal diagnosis of the genetic defect, histidinemia, by immunocytochemical detection of histidase in amniotic fluid epidermal cells; (5) development of a cloned histidase cDNA probe, for eventual investigation of: properties and genesis of the two functional histidase mRNAs; molecular nature of histidase gene transcripts and mRNA processing intermediates; and rates of transcription during development and hormonal control of the histidase gene(s).